Cue-based smoking research has clearly demonstrated that smokers report robust conditioned responding (most often in the form of craving) when exposed to smoking-related stimuli. This work has been used to inform cue-exposure based treatments aimed at eliminating reactivity to cues via extinction training as a means of decreasing the likelihood of relapse. However, past cue-reactivity work is surprisingly limited in what it reveals about how cues affect actual smoking behavior. Two key reasons for this limitation include: (1) focusing primarily on proximal smoking cues (e.g., lit cigarettes, pictorial stimuli of smoking) while ignoring distal cues those less contiguous to the act of smoking (e.g., personal smoking environments and the people around whom one typically smokes), and (2) a strong reliance on self-report measures (e.g., craving) in the absence of measures that assess actual smoking behavior (latency to smoke and ad lib smoking when exposed to cues). In addressing the former limitation, our recent work under a previous exploratory R21 (DA017582) has revealed that smokers respond with equally robust craving to both standard proximal smoking cues and personalized distal smoking cues of environments and people. Additionally, personal environments that signal not smoking and personal people around whom one would never smoke appear to serve a protective function on craving to smoke. However, continuing to study each of these cue type alone fails to offer a complete picture of how cues might function in the real world where such cues more often than not co- exist. In order to examine cues in a manner that more closely mimics how cues are encountered outside of the lab, the proposed research will assess reactivity to both proximal and personal distal cues alone and in combination. Regarding the latter limitation, there is a common assumption that self-report responding to cues (e.g., craving) is directly related to actual smoking behavior; however, this notion is largely untested. Therefore, the second main objective of the proposed studies is to examine how combinations of various cues affect both self-report and behavioral reactivity in smokers, and how those indices of cue responding relate to one another. The proposed studies will result in new understanding of how salient cues that smokers confront in their real lives function alone and in concert to augment or attenuate both their self- report and behavioral cue-reactivity. Moreover, this work will allow for examination of associations and/or disparities between those two key measures of cue reactivity. This work will directly inform new cue-based smoking treatments, both those focused on helping smokers identify and avoid specific smoking triggers, and those aimed at extinguishing urge-responding to reduce relapse post-quit. Furthermore, these procedures may provide a means to index early success following cessation treatment of any kind, as individuals less reactive cognitively or behaviorally to proximal or personal distal cues post-treatment would be expected to be less likely to relapse. PUBLIC HEALTH RELEVANCE: Factors other than nicotine are thought to play key roles in the continuation of smoking and the inability of some smokers to quit. Research has shown that smokers report robust craving when exposed to cues related to past experiences with smoking. Such cues can be both proximal (e.g., cigarette, ashtrays) and distal (e.g., environments and people). This project examines how both types of cues function alone and in combination to affect smokers' thoughts and feelings, as well as their actual smoking behavior. This research will answer important questions about the relationship between different types of cue responding, and will directly inform future behavioral treatments for smoking.